Regulation of LH/FSH expression by secretoglobin 3A2 in the mouse pituitary gland

Yuki Miyano,Reiko Kurotani,Shigeyuki Tahara,Shioko Kimura,Ichiro Sakata,Hiroyuki Abe,Takafumi Sakai

doi:10.1007/s00441-014-1794-z

Abstract

Secretoglobin (SCGB) 3A2 was originally identified as a downstream target for the homeodomain transcription factor NKX2-1 in the lung. NKX2-1 plays a role in the genesis and expression of genes in the thyroid, lung and ventral forebrain; Nkx2-1-null mice have no thyroid and pituitary and severely hypoplastic lungs and hypothalamus. To demonstrate whether SCGB3A2 plays any role in pituitary hormone production, NKX2-1 and SCGB3A2 expression in the mouse pituitary gland was examined by immunohistochemical analysis and RT-PCR. NKX2-1 was localized in the posterior pituitary lobe, whereas SCGB3A2 was observed in both anterior and posterior lobes as shown by immunohistochemistry and RT-PCR. Expression of CCAAT-enhancer binding proteins (C/EBPs), which regulate mouse Scgb3a2 transcription, was also examined by RT-PCR. C/EBPβ, γ, δ and ζ were expressed in the adult mouse pituitary gland. SCGB3A2 was expressed in the anterior and posterior lobes from postnatal days 1 and 5, respectively and the areas where SCGB3A2 expression was found coincided with the area where FSH-secreting cells were found. Double-staining for SCGB3A2 and pituitary hormones revealed that SCGB3A2 was mainly localized in gonadotrophs in 49 % of FSH-secreting cells and 47 % of LH-secreting cells. In addition, SCGB3A2 dramatically inhibited LH and FSH mRNA expression in rat pituitary primary cell cultures. These results suggest that SCGB3A2 regulates FSH/LH production in the anterior pituitary lobe and that transcription factors other than NKX2-1 may regulate SCGB3A2 expression.

Highlights

NKX2-1, called TTF1, TITF1, or T/EBP, is a homeodomain-containing DNA-binding protein that was originally identified as a transcription factor regulating thyroid-specific expression of genes
These results demonstrated that Secretoglobin 3A2 (SCGB3A2) is expressed in anterior and posterior lobes of pituitary gland
These results suggest that transcription factors other than NKX2-1 may be Expression of SCGB3A2 in the neonatal mouse pituitary gland

Summary

Introduction

NKX2-1, called TTF1, TITF1, or T/EBP, is a homeodomain-containing DNA-binding protein that was originally identified as a transcription factor regulating thyroid-specific expression of genes. NKX2-1 is expressed in the lung, thyroid and ventral forebrain during embryogenesis (Guazzi et al 1990; Lazzaro et al 1991; Mizuno et al 1991) and plays a role in morphogenesis of these organs. NKX2-1 suppression by antisense oligonucleotides in vitro using embryonic lung organ cultures, inhibits branching morphogenesis (Minoo et al 1995). Nkx2-1null mice lack the thyroid and pituitary gland and exhibit severe defects in the ventral forebrain, including the hypothalamus and basal ganglia (Kimura et al 1996; Takuma et al 1998; Minoo et al 1999; Sussel et al 1999; Yuan et al 2000). In Nkx2-1-null mice, a Rathke’s pouch rudiment initially forms during pituitary development but is eliminated by programmed cell death before formation of a definitive pouch (Takuma et al 1998). In the diencephalon of the mutant, Fgf expression, which is necessary for activation of a key

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Conclusion